One-step crosslinking type photodynamic high-antibacterial hydrogel and preparation method thereof

Abstract

The application discloses a one-step crosslinking type photodynamic high-antibacterial hydrogel and a preparation method thereof. The hydrogel takes polydopamine, hydrolyzed keratin and polyacrylamide as main raw materials, uses tetramethyl ethylenediamine and potassium persulfate as crosslinking agents, and combines the one-step crosslinking method to prepare a multifunctional composite hydrogel with high antibacterial activity and wound healing promotion, so as to provide a new type of antibacterial hydrogel medical dressing for wound healing promotion by enhancing the mechanical property, adhesion, biocompatibility and photothermal antibacterial property of the hydrogel. The polydopamine prepared from mussels endows the hydrogel with the photothermal antibacterial property, and provides a new antibacterial strategy for the enhanced drug resistance of pathogenic bacteria caused by antibiotic abuse. The keratin is used as the raw material, so that the application reduces the environmental hazards of waste keratin, promotes the development and application of keratin in the biological medicine field, promotes the in-depth excavation of keratin resources, and realizes the high utilization of waste resources.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of composite material preparation, and particularly relates to a multifunctional composite hydrogel with low cost, simple preparation, high antibacterial activity and wound healing promotion and a preparation method thereof. BACKGROUND

[0002] Trauma and trauma infection are common cases in hospitals, and medical dressings can serve as protective barriers to cover wounds, absorb wound exudates and help wound healing. Although traditional dressings have a protective effect on wounds, they cannot meet the current performance requirements of medical dressings in terms of water and air permeability, prevention of bacterial entry and biocompatibility. Biomedical hydrogel dressings are three-dimensional network structure polymer colloidal substances with strong water absorption capacity, adjustable physical and chemical properties, functionalization and similar structural characteristics to extracellular matrix, and have become one of the most competitive wound dressing candidate materials. However, the adhesion, mechanical and antibacterial properties of conventional hydrogels are not satisfactory.

[0003] The present application constructs a one-step cross-linked photodynamic high-antibacterial hydrogel for wound healing, i.e. a composite hydrogel that can achieve photothermal therapy (PTT) antibacterial effect is formed by free radical polymerization of polydopamine (PDA) and polyacrylamide (PAAM). On this basis, Mg 2+ The stability, repeatability and promotion of angiogenesis function of the hydrogel photothermal reaction are improved; the hydrolyzed keratin enhances the adhesion and biocompatibility of the composite hydrogel, and provides a new type of antibacterial hydrogel medical dressing for promoting wound healing. SUMMARY

[0004] The present application is based on hydrolyzed keratin (HK), polydopamine (PDA), magnesium ions and polyacrylamide (PAAM), and a multifunctional composite hydrogel with high antibacterial activity and wound healing promotion is prepared through reasonable material design. The magnesium ions chelate with polydopamine, and the polydopamine is inserted as a macromolecule to convert near-infrared laser radiation into heat, has good antibacterial activity and ROS clearance capacity, and through embedding hydrolyzed keratin, the adhesion and biocompatibility are enhanced, and the wound closure caused by bacterial infection can be effectively promoted. The magnesium chelated semi-interpenetrating network photothermal antibacterial hydrogel is prepared, which has high photothermal conversion performance, adhesion and healing promotion performance. The preparation process of the present application is simple, and the cost is low. It is a new type of medical material with high antibacterial activity and wound healing promotion.

[0005] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0006] A multifunctional hydrogel with high photothermal conversion performance, adhesion and healing performance is designed for bacterial infected wound healing by using the technology and method of material preparation. Magnesium ions are used as photothermal stabilizers, and polydopamine is used as a macromolecule to insert magnesium ion chelation, which converts near-infrared laser radiation into heat, and endows the material with good antibacterial activity and ROS scavenging capacity; by embedding hydrolyzed keratin, the adhesion and biocompatibility are enhanced; and the potential to improve inflammation, reduce oxidative stress and promote angiogenesis is achieved, so as to prepare a magnesium chelated semi-interpenetrating network photothermal antibacterial hydrogel. Specifically, the following steps are included:

[0007] (1) Prepare an ethanol, water and ammonia mixed solution, stir for 30 min;

[0008] (2) Quickly add dopamine hydrochloride and water to the system of step (1), and continuously stir for 24 h;

[0009] (3) The reaction system prepared in step (2) is separated by water washing, and dried by suction filtration to obtain polydopamine powder;

[0010] (4) Add polydopamine powder, hydrolyzed keratin, acrylamide and magnesium chloride to water, and ultrasonic for 1 h;

[0011] (5) Add methylene bisacrylamide to the solution after ultrasonic in step (4) and continuously stir for 1 h;

[0012] (6) Add tetramethyl ethylenediamine and potassium persulfate to the reaction solution prepared in step (5), and slowly stir for 40 s to obtain the multifunctional composite hydrogel with high antibacterial activity and wound healing property.

[0013] Further, in step (1), the amount of ethanol is 40 ml, the amount of deionized water is 90 ml, and the amount of ammonia water (25 wt%) is 1 ml, and the stirring speed is 180~200 rpm.

[0014] In step (2), the amount of dopamine hydrochloride is 0.5 g, the amount of deionized water is 10 ml, and the stirring speed is 180~200 rpm.

[0015] In step (3), the product is washed with deionized water for 3 times, and dried by suction filtration.

[0016] In step (4), the amount of polydopamine powder is 0.03 g, the amount of hydrolyzed keratin is 2 g, the amount of acrylamide is 2 g, the amount of magnesium chloride is 0.012 g, and the amount of deionized water is 20 ml.

[0017] In step (5), the amount of methylene bisacrylamide is 0.01 g, and the stirring speed is 200~250 rpm.

[0018] The amount of tetramethyl ethylenediamine in step (6) is 0.05 ml, the amount of potassium persulfate is 0.05 g, and the stirring speed is 180-200 rpm.

[0019] A one-step cross-linked photodynamic high-antibacterial hydrogel prepared by the above method.

[0020] The present application has the following advantages:

[0021] (1) The present application uses dopamine extracted from natural black melanin of mussels and hair-derived keratin as raw materials, combines the biocompatibility, biodegradability, cell adhesion of natural proteins, and successfully prepares a multifunctional composite hydrogel with high antibacterial activity and wound healing-promoting properties by using a simple one-step cross-linking method.

[0022] (2) The polydopamine extracted from mussels in the present application endows the hydrogel with photothermal antibacterial properties, providing a new antibacterial strategy for the increasing drug resistance of pathogenic bacteria caused by antibiotic abuse.

[0023] (3) The present application uses keratin as raw material, reduces the environmental hazards of waste keratin, promotes the development and application of keratin in the field of biological medicine, promotes the in-depth exploration of keratin resources, realizes the high utilization of waste resources, and promotes the further development of medical wound dressings with low cost and high function.

[0024] (4) The present application introduces magnesium ions into the hydrogel system, enhances the stability and repeatability of the photothermal reaction, improves the red blood cell migration ability, promotes angiogenesis, and improves the healing-promoting ability.

[0025] (5) The present application uses a one-step cross-linking method, the preparation process is simple, the gelation time is short, the preparation process is effectively reduced, the preparation cost is reduced, and the product industrialization is accelerated. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 is the method flowchart of the present application embodiment 3-5.

[0027] Figure 2 is the PDA-HK-PAAM-Mg composite hydrogel prepared by the present application embodiment 3-5. 2+ The actual product diagram of the composite hydrogel.

[0028] Figure 3 is the photothermal effect diagram of the composite hydrogel prepared in the present application embodiment 1-5. DETAILED DESCRIPTION

[0029] In order to make the content described in the present application more convenient to understand, the technical solutions described in the present application are further described below in combination with specific embodiments, but the following examples are only examples of the present application and do not represent the protection scope of the present application, and the protection scope of the present application is subject to the claims.

[0030] Example 1 (HK-PAAM base hydrogel)

[0031] (1) 2 g hydrolyzed keratin, 2 g acrylamide were added into 20 ml deionized water, and ultrasonic was performed for 1 h;

[0032] (2) 0.01 g methylene bisacrylamide was added into the solution after ultrasonic in step (1), and stirring (250 rpm) was continuously performed for 1 h;

[0033] (3) 0.05 ml tetramethyl ethylenediamine and 0.05 g potassium persulfate were added into the reaction solution prepared in step (2), and slow stirring (180 rpm) was performed for 40 s, to obtain a hydrogel.

[0034] Example 2 (PDA-HK-PAAM composite hydrogel)

[0035] (1) a mixed solution of 40 ml ethanol, 90 ml deionized water and 1 ml ammonia water (25 wt%) was prepared, and stirring (200 rpm) was performed for 30 min;

[0036] (2) 0.05 g dopamine hydrochloride and 10 ml deionized water were quickly added into the system in step (1), and stirring (180 rpm) was continuously performed for 24 h;

[0037] (3) the reaction system prepared in step (2) was separated by water washing, and was dried by suction filtration, to obtain a polydopamine powder;

[0038] (4) 0.03 g polydopamine powder, 2 g hydrolyzed keratin and 2 g acrylamide were added into 20 ml deionized water, and ultrasonic was performed for 1 h;

[0039] (5) 0.01 g methylene bisacrylamide was added into the solution after ultrasonic in step (4), and stirring (200 rpm) was continuously performed for 1 h;

[0040] (6) 0.05 ml tetramethyl ethylenediamine and 0.05 g potassium persulfate were added into the reaction solution prepared in step (5), and slow stirring (180 rpm) was performed for 40 s, to obtain a hydrogel.

[0041] Example 3 (PDA-HK-PAAM-Mg 2+ 0.012 composite hydrogel)

[0042] (1) Prepare a mixed solution of 40 ml ethanol, 90 ml deionized water and 1 ml ammonia water (25 wt%), stir (200 rpm) for 30 min;

[0043] (2) Quickly add 0.05 g dopamine hydrochloride and 10 ml deionized water to the system of step (1), continue stirring (180 rpm) for 24 h;

[0044] (3) The reaction system prepared in step (2) is separated by water washing, suction filtration and drying to obtain polydopamine powder;

[0045] (4) Mix 0.03 g of polydopamine powder with 2 g of hydrolyzed keratin, 2 g of acrylamide, and 0.012 g of magnesium chloride in 20 ml of deionized water, and ultrasonic for 1 h;

[0046] (5) Add 0.01 g of methylene bisacrylamide to the solution after ultrasonic in step (4) and continue stirring (200 rpm) for 1 h;

[0047] (6) Add 0.05 ml of tetramethyl ethylenediamine and 0.05 g of potassium persulfate to the reaction solution prepared in step (5), slowly stir (180 rpm) for 40 s, to obtain the one-step cross-linked photodynamic high-antibacterial hydrogel.

[0048] Example 4 (PDA-HK-PAAM-Mg 2+ 0.024 composite hydrogel)

[0049] (1) Prepare a mixed solution of 40 ml ethanol, 90 ml deionized water and 1 ml ammonia water (25 wt%), stir (200 rpm) for 30 min;

[0050] (2) Quickly add 0.05 g dopamine hydrochloride and 10 ml deionized water to the system of step (1), continue stirring (180 rpm) for 24 h;

[0051] (3) The reaction system prepared in step (2) is separated by water washing, suction filtration and drying to obtain polydopamine powder;

[0052] (4) Mix 0.03 g of polydopamine powder with 2 g of hydrolyzed keratin, 2 g of acrylamide, and 0.024 g of magnesium chloride in 20 ml of deionized water, and ultrasonic for 1 h;

[0053] (5) Add 0.01 g of methylene bisacrylamide to the solution after ultrasonic in step (4) and continue stirring (200 rpm) for 1 h;

[0054] (6) To the reaction solution prepared in step (5), 0.05 ml of tetramethyl ethylenediamine and 0.05 g of potassium persulfate were added, and slow stirring (180 rpm) was carried out for 40 s to obtain the one-step cross-linked photodynamic high-antibacterial hydrogel.

[0055] Example 5 (PDA-HK-PAAM-Mg 2+ 0.036 composite hydrogel

[0056] (1) A mixed solution of 40 ml of ethanol, 90 ml of deionized water and 1 ml of ammonia water (25 wt%) was prepared, and stirring (200 rpm) was carried out for 30 min;

[0057] (2) 0.05 g of dopamine hydrochloride and 10 ml of deionized water were quickly added to the system of step (1), and continuous stirring (180 rpm) was carried out for 24 h;

[0058] (3) The reaction system prepared in step (2) was separated by water washing, and was dried by suction filtration to obtain polydopamine powder;

[0059] (4) 0.03 g of polydopamine powder was mixed with 2 g of hydrolyzed keratin, 2 g of acrylamide, and 0.036 g of magnesium chloride in 20 ml of deionized water, and was ultrasonicated for 1 h;

[0060] (5) 0.01 g of methylene bisacrylamide was added to the solution after ultrasonication in step (4), and continuous stirring (200 rpm) was carried out for 1 h;

[0061] (6) To the reaction solution prepared in step (5), 0.05 ml of tetramethyl ethylenediamine and 0.05 g of potassium persulfate were added, and slow stirring (180 rpm) was carried out for 40 s to obtain the one-step cross-linked photodynamic high-antibacterial hydrogel.

[0062] Photothermal effect determination:

[0063] Gel-1, Gel-2, Gel-3, Gel-4 and Gel-5 (corresponding to Examples 1-5) hydrogels were irradiated with 808 nm NIR laser (1.5 W / cm −2 , 10 min). At the same time, an infrared imaging device was used to observe the temperature change and obtain a photothermal image.

[0064] PDA maintains excellent photothermal effect, and PDA nanoparticles are introduced into the hydrogel system to start photothermal therapy. Figure 3The photothermal ability of the gels 1-5 is shown in FIG. 2. According to the infrared thermal images, the color of the gels 2-5 becomes brighter in 10 minutes, the color of the gel-2 rises the fastest, the temperature rises the most, the change speed of the gels 3-5 is significantly slower than that of the gel-2, and the temperature change range is reduced, while the color of the gel-1 does not change significantly, and the temperature remains at about 21℃. The above phenomenon is mainly because the introduction of PDA nanoparticles into the gels 2-5 may trigger the photothermal effect. The magnesium ion acts as a photothermal stabilizer, making the photothermal effect more stable. The results show that under the irradiation of 808 nm, the final temperatures of the gels 2-5 are 53℃, 42℃, 41℃ and 46℃, respectively, and the final temperature of the gel 3-5 is about 45℃, which belongs to mild photothermal antibacterial and is more suitable for the healing of infectious wounds.

[0065] The above description is only the preferred embodiment of the present application, and any equivalent changes and modifications made within the scope of the patent application of the present application shall be included in the scope of the present application.

Claims

1. A method for preparing one-step cross-linked photodynamic high-antibacterial hydrogel, characterized in that: Comprising the following steps: (1) preparing a mixed solution of ethanol, water and ammonia, and stirring; (2) quickly adding dopamine hydrochloride and water to the system of step (1) and continuously stirring; (3) separating the reaction system prepared in step (2) by water washing, and drying by suction filtration to obtain polydopamine powder; (4) adding polydopamine powder, hydrolyzed keratin, acrylamide and magnesium chloride into water and ultrasonicating; (5) adding methylene bisacrylamide to the solution after ultrasonicating in step (4) and continuously stirring; (6) adding tetramethyl ethylenediamine and potassium persulfate to the reaction solution prepared in step (5) and slowly stirring to obtain a multifunctional composite hydrogel with high antibacterial activity and wound healing promotion; In step (1), the amount of ethanol is 40 mL, the amount of deionized water is 90 mL, the amount of ammonia is 1 mL, the stirring speed is 180-200 rpm, and the stirring time is 30 min; In step (2), the amount of dopamine hydrochloride is 0.5 g, the amount of deionized water is 10 mL, the stirring speed is 180-200 rpm, and the continuous stirring time is 24 h; In step (4), the amount of polydopamine powder is 0.03 g, the amount of hydrolyzed keratin is 2 g, the amount of acrylamide is 2 g, the amount of magnesium chloride is 0.012 g, the amount of deionized water is 20 mL, and the ultrasonicating time is 1 h; In step (5), the amount of methylene bisacrylamide is 0.01 g, the stirring speed is 200-250 rpm, and the continuous stirring time is 1 h; In step (6), the amount of tetramethyl ethylenediamine is 0.05 mL, the amount of potassium persulfate is 0.05 g, the stirring speed is 180-200 rpm, and the slow stirring time is 40 s.

Images